The key genes, NOX4, CCDC80, COL1A2, HTRA1, and KLHL29 were significantly expressed in DCM, with KLHL29 and HTRA1 especially closely associated with the immune response, which might be markers for obesity-induced DCM and be potential avenues for exploration in immunotherapy. Here, HTRA1 is linked to obesity due to melanocortin 4 receptor deficiency.