The future of Lake Baikal’s biodiversity is uncertain in response to climate change. Unlike its diverse benthos, Lake Baikal’s zooplankton is species poor, with up to 96% of its biomass being composed of a single Calanoid copepod species, Epischura baikalensis. This study characterizes the genetic differentiation and differential gene expression of E. baikalensis. Using partial-transcriptome sequences obtained by 454 Rosche and Illumina sequencing technologies, the genetic differentiation at inferred single nucleotide polymorphism (SNP) sites and differential gene expression in populations sampled from various parts of the lake were analyzed. The functional genomics of genes showed significant differential expression among the lake’s regions with some genes being highly up-or down-regulated. High genetic differentiation among regions suggests isolated subpopulations. Moreover, significantly differentially expressed transcripts were significantly more genetically differentiated than transcripts exhibiting no differential expression. These results suggest high potential phenotypic plasticity and adaptability in response to climate change, e.g., temperature.