Ongoing ocean warming due to climate change poses new challenges for marine life and its exploitation. We have used transcriptomics to find genetically-based responses to increased temperature in natural populations of the marine clam Ruditapes decussatus living along parallel thermal gradients in southern Europe. Clams of the Atlantic and West Mediterranean races were collected in a northern (cool) and a southern (warm) localities. The animals were kept in running seawater in the warm, Atlantic southern locality for a 15-week period, during which water temperature raised to typical southern European summer values. After this period, the expression profile was obtained for a total of 34 clams and 11,025 probes by means of an oligonucleotide microarray. We found distinct transcriptional patterns for each population based on a total of 553 differentially expressed genes (DEG), indicating innate differences which probably have a genetic basis. Race and latitude contributed significantly to gene expression differences, with very different sets of DEG. A gene ontology analysis showed that races differed mainly at genes involved in ribosomal function and protein biosynthesis, while genes related to glutathione metabolism and ATP synthesis in the mitochondria were the most outstanding as to north/south transcriptional differences.