Muscular dystrophies (MDs) are a group of genetic disorders characterized by progressive muscle degeneration and strongly accompanied by fibrosis. The spectrum of phenotypic manifestations in MDs emerges from the complex interplay among distinct cell types constituting skeletal muscle. To elucidate the molecular mechanisms underpinning compromised muscle function in MDs, we conducted extensive transcriptomic profiling in muscles of a mouse model representative of the severe LAMA2-related muscular dystrophy (LAMA2 MD), the dyW/dyW mouse. Our analysis unveiled the downregulation of Wif1, an inhibitor of the Wnt pathway, in the muscles of dyW/dyW mice. Through the use of single nucleus-RNAseq, we found that Wif1 is expressed in tenocytes. Most importantly, Wif1 overexpression mitigated fibrotic disease manifestations in the muscles of dyW/dyW mice. Collectively, our findings provide strong evidence for a pivotal role of the Wnt pathway in MD progression, and they emphasize the significant impact of non-muscle cell populations on disease manifestations, suggesting potential targets for therapeutic development in MDs.