Knowledge of which genes and pathways are affected by inbreeding may help understanding the genetic basis of inbreeding depression, the potential for purging (selection against deleterious recessive alleles) and the transition from outcrossing to selfing. Arabidopsis lyrata is a predominantly self-incompatible perennial plant, closely related to the selfing model species A. thaliana. To examine how inbreeding affects gene expression, we compared the transcriptome of experimentally selfed and outcrossed A. lyrata originating from two Scandinavian populations that express similar inbreeding depression for fitness (∂≈0.80). The number of genes significantly differentially expressed between selfed and outcrossed individuals were 2.5 times higher in the Norwegian population (≈500 genes) than in the Swedish population (≈200 genes). In both populations a majority of genes were up-regulated upon selfing (≈80%). Functional annotation analysis of the differentially expressed genes showed that selfed offspring were characterized by (i) up-regulation of stress-related genes in both populations, and (ii) up-regulation of photosynthesis-related genes in Sweden but down-regulation in Norway. Moreover, we found that reproduction- and pollination-related genes were affected by inbreeding only in Norway. We conclude that inbreeding causes both general and population-specific effects. The observed common effects suggest that inbreeding generally up-regulates rather than down-regulates gene expression and affects genes associated with stress response and general metabolic activity. Population differences in number of affected genes and in effects on the expression of photosynthesis-related genes show that the genetic basis of inbreeding depression can differ between populations with very similar levels of inbreeding depression.