D7 xenomitochondrial mice were subjected to a battery of neuromuscular and motor assessments along with mitochondrial oxygen consumption and gene expression analyses. In some motor tests, D7 xenomitochondrial mice displayed slightly enhanced performance over wildtype mice. No differences were seen in oxygen consumption analysis. Gene expression studies in xenomitochondrial mice revealed changes in mtDNA transcription compared to wildtype controls. No changes in the expression of nuclear encoded respiratory complexes were observed, but changes were seen in several other nuclear encoded genes related to nuclear transcriptional regulation. These results indicate that mismatches occasioned by the presence of xenomitochondrial genomes led to compensatory transcriptional changes.