The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) is a critically endangered small odontocete species, mainly distributed in the middle and lower reaches of the Yangtze River, Poyang Lake, and Dongting Lake. Under the influence of human activities, many factors are threatening the survival and reproduction of YFPs in their natural habitat. Ex situ conservation is of great significance to strengthen the rescuing conservation of YFPs by providing suitable alternative habitats and promoting the reproduction and growth of the ex situ population. To reveal the differences in gene expression of YFPs in natural and ex situ protected waters, and to investigate the effects of environmental factors on YFPs and their mechanisms, we performed transcriptome sequencing for blood tissues of YFPs collected from natural waters and ex situ protected waters. Using RNA-seq we identified 4613 differentially expressed genes (DEGs), of which 4485 were up-regulated and 128 were down-regulated in the natural population. GO analysis showed that DEGs were significantly enriched in entries related to binding, catalytic activity, and biological regulation; KEGG analysis showed that DEGs were enriched mainly in signal transduction, endocrine system, immune system, and sensory system-related pathways. Further analysis revealed that water pollution in natural waters may affect the hormone secretion of YFPs by altering the expression pattern of endocrine genes, thus interfering with normal endocrine activities; noise pollution may induce oxidative stress and inflammatory responses in YFPs, thus impairing the auditory function of YFPs. This study provides a new perspective for further research on the effect of habitat conditions on the YFPs and suggests that improving the habitat environment may help in the conservation of YFPs.