Large annual escapees of farmed Atlantic salmon enhance the risk of extinction of wild populations through genetic and ecological interactions. Recently, we documented evolutionary change in gene transcription between farmed and wild Atlantic salmon after only five generations of artificial selection. While differences for most quantitative traits are expected to gradually dilute through repeated backcrossing to wild populations, the genetic basis of gene transcription has been shown to be largely nonadditive and hybrid crosses may display unexpected inheritance patterns. This makes it difficult to predict to what extent interbreeding between farmed and wild individuals will change the genetic makeup of wild salmon populations. Here, we compare the genome-wide gene transcription profiles of Norwegian wild salmon to that of a second generation hybrid cross [backcross: (Farmed X Wild) X Wild]. Over 6% (298, q-value < 0.01) of the detected genes exhibited highly significantly different transcription levels, and the range and average magnitude of those differences was strikingly higher than previously described between pure farmed and wild strains. Most differences appear to result from nonadditive gene interactions. These results suggest that interbreeding of fugitive farmed salmon and wild individuals could substantially modify the genetic control of gene transcription in natural populations exposed to high migration from fish farms, resulting in potentially detrimental effects on the survival of these populations. This further supports the idea that measures to considerably reduce the number of escaped farmed salmon and their reproduction in the wild are urgently needed.