AbstractIn the northern hemisphere, the spatial structure of many taxa has been shaped by migration patterns after the last glaciation, and phylogeography based on mtDNA variation may reflect the post-glacial demography. The mtDNA lineages are expected to differ in their adaptations to local conditions but little is known about the impact of these conditions on functional genetic variation. Here, we answer this question through an analysis of geographic variation and selection patterns in seven innate immunity genes in free-living bank volesMyodes glareolusfrom 10 localities across species range assigned to different lineages based on mtDNA. We found clear discrepancies between population structure in mtDNA and each of the studied innate immunity genes. There was no uniform pattern of spatial variation at immunity loci, they differed in the levels of polymorphism, and the results of neutrality tests were not consistent over loci. Each locus comprised a few common haplotypes shared between mitochondrial lineages and studied locations, plus numerous haplotypes unique for each studied site. Our results suggest that the diversity of innate immunity genes cannot be explained solely in terms of demographic processes, and that the observed polymorphism may be attributed to local selection. The strength and direction of selection differed between loci, even within the same gene family, which underlines how crucial it is to take a complex approach while studying the selection patterns acting on immune-related genes.