Hucho bleekeri is a glacial relict and critically endangered fish restricted to the Yangtze River drainage in China. The lack of basic genomic information and immune characteristics will hinder the way toward protecting this species. In the present study, we conducted the first transcriptome analysis of H. bleekeri using the combination of SMRT and Illumina sequencing technology. Transcriptome sequencing generated a total of 93,330 non-redundant full-length unigenes with a mean length of 3072 bp. A total of 92,472 (99.08%) unigenes were annotated in at least one of the Nr protein, Swiss-Prot, KEGG, KOG, GO, Nt and Pfam databases. KEGG analysis showed that a total of 7240 unigenes belonging to 28 immune pathways were annotated to the immune system category. Meanwhile, differentially expressed genes between mucosa-associated tissues (skin, gill and hindgut) and systemic-immune tissues (spleen, head kidney and liver) were obtained. Importantly, genes participating in diverse immune signalling pathways and their expression profiles in H. bleekeri were discussed. In addition, a large number of long non-coding RNAs (lncRNAs) and simple sequence repeats (SSRs) were obtained in the H. bleekeri transcriptome. The present study will provide basic genomic information for H. bleekeri and for further research on analysing the characteristics of both the innate and adaptive immune systems of this critically endangered species.