SummaryIndigenous cattle breeds in northern Eurasia have adapted to harsh climate conditions. The local breeds are important genetic resources with cultural and historical heritages, and therefore, their preservation and genetic characterization are important. In this study, we aim to identify genes and biological processes that are important for their adaptation to the cold and harsh conditions. For this purpose, we profiled the whole-blood transcriptome of two native breeds and one commercial breed using high-throughput RNA sequencing. More than 15,000 genes were identified, of which 2, 89, and 162 genes were significantly upregulated exclusively in Northern Finncattle, Yakutian cattle and Holstein cattle, respectively. The functional classification of these significantly differentially expressed genes identified several biological processes and pathways related to signalling mechanisms, cell differentiation, and host-pathogen interactions that, in general, point towards immunity and disease resistance mechanisms. The gene expression pattern observed in Northern Finncattle was more similar to that of Yakutian cattle, despite sharing similar living conditions as the Holstein cattle included in our study. In conclusion, our study identified unique biological processes in these breeds that help them to adapt and survive in sub-arctic environments.