Parasitic infections are ubiquitous, but the consequences to hosts can vary substantially. Variation in the consequences of infection can be related to individual differences in the use of two parasite defense strategies, resistance and tolerance. Resistance entails reducing parasite burden by removing parasites or restricting parasite reproduction. Tolerance involves minimizing the costs associated with a given parasite burden. Genetic variation, environmental conditions, and life history stage can contribute to variation in resistance and tolerance, but the physiological mechanisms that underlie investment in each strategy are not well understood. I proposed that glucocorticoid hormones, which mediate responses to challenges in the physical and social environment in vertebrates, might alter host investment in resistance and tolerance (Chapter I). Glucocorticoids influence a suite of physiological processes including immune function, resource allocation, and tissue growth, all which could alter resistance and tolerance. Using a combination of observational and experimental studies, I test the hypothesis that glucocorticoids mediate resistance and tolerance to infection in red-winged blackbirds (Agelaius phoeniceus) infected with Haemosporidians, including malaria (Plasmodium) and malaria-like (Haemoproteus and Leucocytozoon) parasites. I performed a medication experiment (Chapter II) to identify the physiological consequences of Haemosporidian infection and explored the relationships between glucocorticoids and parasite resistance and tolerance in both an observational field study and a hormone manipulation experiment (Chapters III and IV). Medication treatment effectively reduced Plasmodium burden, increased hematocrit and hemoglobin, and reduced the rate of red blood cell production (Chapter II). In an observational field study (Chapter III), red-winged blackbirds with higher plasma glucocorticoid concentrations maintained higher hematocrit than expected for their parasite burdens, suggesting a positive association between glucocorticoids and tolerance. In this study, I found no support for a relationship between glucocorticoids and resistance. However, experimental elevation of glucocorticoids (Chapter IV) yielded nearly opposite results: the higher of two doses of glucocorticoids increased Plasmodium burdens and caused a decrease in body mass with increasing parasite burden, indicative of a decrease in tolerance. I discuss possible causes of the differences in our observational and experimental studies and the implications of my work for future studies of individual variation in parasite tolerance (Chapter V). / Ph. D. / Why does a cold leave some people bed-ridden, while others can go about their day with only a few sniffles? We can easily see that people react differently when they encounter an infection, but it is not clear why. When faced with an infection, there are two main defense strategies: resistance and tolerance. Resisting infection means reducing the number of parasites or pathogens in the body. Tolerance, on the other hand, refers to reducing the damage or costs that occur during infection. For example, an individual could resist a cold by using the immune system to kill off viruses. If someone tolerates a cold, they might not feel very sick, despite the presence of viruses. Individuals that are more tolerant could be suppressing their own immune response, which can cause the inflammation that leads to a stuffy nose, or these individuals might be repairing damage caused by the virus. Individuals can vary in the extent to which they resist or tolerate infection, but we do not know why this variation exists. In this dissertation, I investigate how the hormones associated with physiological stress might influence resistance and tolerance to malaria and malaria-like parasite infections in red-winged blackbirds. First, I performed a study in which I treated birds infected with a blood-borne parasite with anti-malarial medication to identify the costs of chronic infection. Then I observed the relationships between glucocorticoids (the hormones associated with physiological stress) and estimates of resistance and tolerance in wild red-winged blackbirds. Finally, I used hormone implants to increase stress hormone concentrations in birds held in aviaries, and assessed whether the implants caused changes in resistance and/or tolerance. My results suggest that chronic malaria infection can 5 damage or destroy red blood cells and birds compensate by increasing the rate of blood cell production. In wild red-winged blackbirds, birds with higher concentrations of stress hormones were able to maintain a higher proportion of red blood cells in the blood for a given parasite burden, suggesting they were more tolerant. Stress hormone levels were not associated with the total number of parasites, and thus, we have no evidence for a relationship between the hormones and resistance. When we increased the hormone levels in the aviary experiment, we found nearly opposite results. A high dose of stress hormones caused an increase in the number of parasites and increased the cost of infection. In this dissertation, I discuss possible explanations for the different results in the observational study and the experiment and suggest avenues for future studies.

Life-history strategies are adaptations in behavior, physiology, and anatomy that influence survival and reproductive success. Variation in life-history strategies is often determined by adaptations to environmental conditions and trade-offs with sexually-selected signals. One of the aspects controlling life-history trade-offs is the endocrine system. Testosterone is a hormone that mediates several key aspects of male reproduction, yet little is known about the causes and consequences of variation in testosterone. Using rufous-collared sparrows (Zonotrichia capensis), a Neotropical songbird with a wide distribution, I explored geographical patterns of variation in testosterone levels and infection by haemosporidians, a type of blood parasite. I found that testosterone did not vary with elevation, nor predict haemosporidian infection, but males in breeding condition were more likely to be infected (Chapter I). High levels of testosterone have been associated with an increased number of sexual contacts and can suppress the immune response, thus it may increase the risk of sexually transmitted infections. By studying the communities of bacteria that reside in the cloaca of birds, I found that they were different depending on testosterone levels, and that high-testosterone males had higher relative abundance of Chlamydiae, a class of intracellular pathogens (Chapter II). During the breeding season there is an increase in physical contacts among individuals, testosterone levels increase in males, and there are additional energetic demands, all of which can increase exposure to bacteria or facilitate infection. I compared the cloacal microbiome of the same individuals between breeding and non-breeding seasons, and found that in males, but not in females, bacterial richness and phylogenetic diversity increased when birds were in reproductive condition. This suggested that the cloacal microbiome in birds is dynamic and responsive to breeding condition and sex of the host (Chapter III). Lastly, I synthesized the most relevant findings and suggested directions for future work (Chapter IV). I conclude that variation in testosterone is not always associated with immune suppression, and that the links among reproductive physiology, behavior, and the microbiome can provide insight into the evolution of life-history strategies. / Ph. D.

Life-history is the study of all the different stages of life that affect reproductive success and survival between the birth and death of an organism. The reproductive output of an organism is constrained by many things including time, resource, disease agents and environmental conditions. In addition, lineage-specific traits and the limitations of the physiological systems can limit how an organism responds to ecological processes, and thus constrains the variation of life histories represented in nature. Central to the theory of life history are the trade-offs that organisms make during their lifetime to maximise their reproductive potential. In this thesis, I focus on the effect of haemosporidian blood parasites on host life history, in relation to the glucocorticoid response and environmental conditions. The host study species is a population of collared flycatchers (Ficedula albicollis), a species that provides bi-parental care, located in the south of Gotland. We show that nestling condition predicts parasite infection and that parasite-mediated selection can start early on in the birds’ life. We also found a link between Lower levels of glucocorticoids and parasite infection, which might indicate a trade-off between immunity and reproductive effort. Adult birds’ upregulated glucocorticoids in response to an increase in reproductive effort and a predictable change in energy demand during reproduction. I also show that glucocorticoids respond to changing environmental conditions. These results together accentuate the importance of the plasticity of the glucocorticoid response to reproductive success. Moreover, higher levels of hormone during reproduction predicted survival to the next breeding season. In nestlings, glucocorticoid levels increased as a consequence of parent infection status and an increase in reproductive effort. Overall, our results indicate that the glucocorticoid response is context dependent. Finally, female collared flycatchers might pay a fitness cost as a consequence of parasite infection, but can still reproduce successfully suggesting that they can tolerate the parasite. To further our understanding of costs related to parasite infection, we must understand better the mechanisms that enable the host to tolerate infection. This study indicates that glucocorticoids provide a useful tool to detect how wild birds respond to predictable and unpredictable challenges.