Red-sided garter snakes are the most northerly living reptile in the western hemisphere. These terrestrial ectotherms experience extreme fluctuations in temperature, emerging after brumation with body temperatures near 0 ̊C and ambient temperatures often 20-30 ̊C. Utilizing basking behaviors, body temperatures can rapidly rise from just above 0 ̊C to near 35 ̊C. While environmental temperatures vary greatly, these snakes use behavioral thermal regulation to maintain body temperatures in an ideal thermal zone when active. This behavioral thermal regulation is effective within a range of temperatures, however when the temperature exceeds those boundaries behavior is not sufficient alone to maintain homeostasis and they become inactive. The bounds of these thermal conditions were determined experimentally using the loss of righting response for both high and low temperatures. RNA-seq was used to characterize the transcriptional response to acute thermal stress. Heart, liver, testis, and brain tissues were used to capture the transcriptional response to both acute cold stress and heat stress and have been analyzed for differential gene expression analysis and functional gene ontology enrichment. Over 90 genes were found to be differentially expressed when treatment transcriptional activity was compared to transcriptional activity for control conditions. The top 3 differentially expressed genes were heat shock proteins and gene ontology analysis shows that the primary gene response is to thermal stress. Understanding both the physiological boundaries of the thermal conditions that these snakes can survive, as well as the transcriptional strategies that they employ to help them survive creates a better understanding of how these animals thrive in a dynamic thermal environment.