Marine pelagic species are being increasingly challenged by environmental change. Their ability to persist will depend on their capacity for physiological acclimatization. Little is known about limits of physiological plasticity in key species at the base of the food web. Here we investigate the capacity for acclimatization in the copepod Neocalanus flemingeri, which inhabits the Gulf of Alaska, a heterogeneous and highly seasonal environment. RNA-Seq analysis of field-collected pre-adults identified large regional differences in expression of genes involved in metabolic and developmental processes and response to stressors. We found that lipid synthesis genes were up-regulated in individuals from Prince William Sound and down-regulated in the Gulf of Alaska. Up-regulation of lipid catabolic genes in offshore individuals suggests they are experiencing nutritional deficits. The expression differences demonstrate physiological plasticity in response to a steep gradient in food availability. Our transcriptional analysis reveals mechanisms of acclimatization that likely contribute to the observed resilience of this population.