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 the 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) by combining whole-genome sequences with fitness data. the impacts of genomic erosion in remnant populations were reversed in an admixed breeding program, suggesting the 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. longimembris pacificus). Historically distributed along an ~200-km stretch of coastal Southern California (22, 23), the Pacific pocket mouse occupied 30 known localities in the 1930s (Fig. 1A), but habitat destruction led to its widespread extirpation, and it was thought to be extinct for 20 years before its rediscovery in 1993 (22). Three known remnant populations persist at Dana Point (12 ha), Santa Margarita (885 ha), and South San Mateo (105 ha) (Fig. 1A), isolated by geography and urban development (22). We generated whole-genome sequence data for 468 Pacific pocket mice to examine the potential impacts of genetic rescue as a conservation tool.