Species that undertake altitudinal migrations are exposed to a considerable seasonal variationin oxygen levels and temperature. How they cope with this was studied in a population of greattit (Parus major) that breeds at high elevations and winters at lower elevations in the easternHimalayas. Comparison of population genomics of high altitudinal great tits and those living inlowlands revealed an accelerated genetic selection for carbohydrate energy metabolism (aminosugar, nucleotide sugar metabolism and insulin signaling pathways) and hypoxia response (PI3K-akt,mTOR and MAPK signaling pathways) in the high altitudinal population. The PI3K-akt, mTOR andMAPK pathways modulate the hypoxia-inducible factors, HIF-1α and VEGF protein expression thusindirectly regulate hypoxia induced angiogenesis, erythropoiesis and vasodilatation. The strategiesobserved in high altitudinal great tits differ from those described in a closely related species onthe Tibetan Plateau, the sedentary ground tit (Parus humilis). This species has enhanced selectionin lipid-specific metabolic pathways and hypoxia-inducible factor pathway (HIF-1). Comparativepopulation genomics also revealed selection for larger body size in high altitudinal great tits.