Musk, secreted by adult male forest musk deer, is a kind of precious Chinese traditional medicine for treating cardiovascular, cerebrovascular and neurogenic diseases. However, a lack of knowledge on musk biosynthetic mechanism and limited musk deer population have seriously hindered the development of the musk industry. Fortunately, given that muskrat musk has similar constituents and pharmacological action with deer musk, muskrat is an ideal model animal for exploring musk biosynthetic mechanism. To explore the biosynthetic mechanism of muskrat musk, in the current study, transcriptomic analysis in the liver, kidney and musk glands of male muskrats between musk secreting and non-musk secreting stages was conducted. The findings indicated that the role of muskrat liver on musk biosynthesis was altering sugar, lipid and amino acid metabolism as well as producing basic resources to support musk glands. Moreover,
Tigar
,
Slc11a2
,
Gpt
,
Hmgcr
,
Slc27a4
, and
Elovl1
were identified as candidate genes for musk biosynthesis via a remotely controlled process. Expression of the
Tigar
,
Slc11a2
, and
Gpt
genes in the liver are downregulated to support the production of musk in muskrat musk gland. And the
Hmgcr
,
Slc27a4
, and
Elovl1
genes in the musk gland participate in muskrat musk synthesis by influencing lipid metabolism in the musk secreting period. This study provided novel insights into the musk biosynthetic pathway in muskrat by transcriptomic analysis and preliminarily suggested the remote control of metabolism from the liver to musk gland during musk biosynthesis, which was useful to further understanding the musk biosynthetic process and improve musk production in the future.