Fitness benefits of genetic rescue despite chromosomal differences in an endangered pocket mouse

Two thirds of Earth’s species have undergone population declines, leaving many vulnerable to genomic erosion and inbreeding depression. Genetic rescue can boost fitness of small populations, but perceived risks of outbreeding depression can limit its use. We quantified these trade-offs in hundreds of endangered Pacific pocket mice (Perognathus longimembris pacificus), combining whole genome sequences with fitness data. The impacts of genomic erosion in remnant populations were reversed in an admixed breeding program, suggesting potential benefits of genetic rescue. However, differences in chromosome numbers increase the risk of genetic incompatibilities. Fitness analyses suggested that although admixed karyotypes may have reduced fertility, non-admixed mice with low heterozygosity and high genetic load had even lower fitness, pointing to a greater risk of extinction if populations remain isolated. We use Hi-C to characterize large-scale structural variation in the genomes of 17 Pacific pocket mouse individuals from three wild remnant populations.