The growth of aquaculture industry, and in particular of salmonids, has dramatically increased in the last decades to supply the growing worldwide demand for fish products. The expansion of aquaculture needs a good management to ensure the sustainability of this activity. In particular, improving feeds for aquaculture to enhance health and performance of reared fish is imperative for this industry. Molecular biological approacches can help interpret responses to new diets and immune responses. Ubiquitin ligases (UbE3s) play a pivotal role in the ubiquitin proteasome pathway of protein degradation and are markers that could be linked to health and performance of fish. Six UbE3s were characterized, 4 are related to muscle catabolism and two involved in NF-kB activation. Atrogin-1 and MuRF genes were increased following food deprivation and a proinflammatory stimulation. MULAN and Mul1b, are mitochondrial activators of NF-kB and the expression of both genes was increased following a proinflammatory immune challenge both in vivo and in vitro. These genes have been used as markers in dietary traits to understand responses. A transcriptome study using Atlantic salmon fed a commercially available functional feed designed for optimal health status compared to a standard feed was performed. Both the liver and muscle were chosen for the transcriptomic analysis. In liver, a number of process were found down regulated, including protein turnover and innate immunity. No significant alterations were found in muscle. To determine the effect of a high plant protein diet (PP), compared to a marine profile diet (MP) in Atlantic a transcriptomic analysis was performed. Fish grew equally well on both diets and no significant histological differences were seen in intestine. The PP diet induced tissue specific changes in gene expression, with the mid intestine showing activation of the adaptive immune response and protein turnover. In liver cell proliferation and apoptosis indicate cellular reorganization and also a general suppression of processes such as immune response was observed. In contrast muscle tissue showed reduced protein metabolism and decrease in immune gene expression suggesting less energy expenditure in this tissue. To assess fish response to Piscirickttsia salmonis, the etiological agent of the salmonid rickettsial seeticemia (SRS), a transcriptomic analysis was carried out. P. salmonis infection has profound effects on transcription in the head kidney, liver and muscle of salmon. Head kidney, liver and muscle tissue showed a decrease in expression of mRNAs related to acquired immune function indicating the pathogen is down regulating this response controlled in part by the inhibition of the G-protein signalling pathway, whereas the innate immune response was increased in head kidney. Liver and muscle also responded, including specific responses in each tissue type. These results improve understanding of the mechanisms by which this bacterium survives and replicates within host cells and may assist selection of molecular biomarkers useful for the development of a diagnostic tools, vaccines and therapeutants for the aquaculture industry. Using markers selected from the previous experiments, the effect of four different diets, a marine profile diet (MP/FO), a plant protein diet (PP/FO), a vegetable oil diet (MP/VO) and PP/VO diet, in Atlantic salmon were examined. Markers for protein and lipid metabolism and immune response were studied in mid intestine, liver and muscle of fish fed for 77 days the four diets. Small but significant changes were observed, but despite of this, fish fed all the four diets showed similar growth rates. Moreover, to study the possible effect of the diets on fish health, the expression of specific SRS markers was studied in head kidney and liver of fish fed the four diets and infected with P. salmonis. The SRS challenge demonstrated that all groups of fish were able to respond efficiently to the pathogen. In conclusion, these new diets may represent good alternatives to fish meal (FM) and fish oil (FO) diets indicating that a replacement of marine diets with vegetable sources is possible in Atlantic salmon without affecting neither fish growth and performance nor the health of fish. The findings presented in this thesis suggest that E3 ligases are good molecular markers, allowing to study performance and health of fish following feeding trial and pathogen challenge. In addition, transcriptomic analysis performed to select further key molecular markers involved in a variety of processes and improved our knowledge of fish physiology and immunology, providing useful information for the development of new alternative diets for aquaculture.