## 4 Discussion
Of these, several genes showed similar expression patterns in both groups, such as bcl2 apoptosis regulator (_bcl2_), caspase 8 (_casp8_), _ctsl1_, gamma-aminobutyric acid receptor-associated protein-like 1 and 2 (_gabarap1l_), rb1 inducible coiled-coil 1 (_rb1 cc1_) and _calocco1_. Members of the Bcl2 family proteins such as antiapoptotic _bcl2_ suppress apoptosis, whereas _casp8_ is an extrinsic apoptosis initiator and necroptosis suppressor [80]. Other genes were significantly increased at 2 dpi and then decreased to the control level, such as rkb inhibitor alpha (_nfkba_), jun proto-oncogene ap-1 transcription factor subunit (_jun_), which is involved in apoptosis, and glutamine synthetase (_glul_), which is involved in necroptosis. Moreover, _nfka_, which stimulates macrophage activity in fish [81] and activates both necroptosis and apoptosis, was also up-regulated after 2 dpi, and then its expression decreased. Previously, a strong expression of _nfka_ was noticed at 3 days post infection by _A. salmonicida achromogenes_ in the head kidney of Artic charr (_Salvelinus alpinus_) [82]. Otherwise, the expressions of other genes involved in apoptosis such as _cyc_ and dynein light chain lc8-type 1 (_dynll1_) were similar to the uninfected fish at 2 dpi and then raised at 6 dpi. Apoptosis and necroptosis are vital parts of the host immune defense mechanism, which cleans up damaged cells and plays a role in host-pathogen interactions [83]. Further, the ferrotposis process was enriched in moribund fish. Ferroptosis is a Reactive Oxygen Species (ROS)--a dependent form of inflammatory cell death associated with iron accumulation and lipid peroxidation--that induces an inflammatory immune response in macrophages [84]. Between the genes involved in the regulation of ferrotposis, solute carrier family 3 member 2 (_slc3a2_), spermidine/spermine n1-acetyltransferase 1 (_sat1_), microtubule-associated protein 1 light chain 3 beta (_map1 lc3b_), ferritin heavy chain 1 (_fhl1_), heme oxygenase 1 (_hmox1_), _alox5 ap_, acyl-coa synthetase long chain family member 1 (_acs1l_), _ptsg2_ and nfe2 like bzip transcription factor 2 (_nf62 le_) were up-regulated at two days post infection in rainbow trout. In accordance with this, the raised expressions of ferritin and _hmox1_ and the induction of ferrotposis in response to _E. coli_ infection were studied in grass carp (_Ctenopharyngdon itella_) [85]. Altogether, programmed cell death processes are critical to maintain homeostasis and plays a role in immune response. The cytoskeleton and extracellular matrix (ECM) play essential roles in cell structure and function. A cytoskeleton is a cellular frame inside a cell, and it plays a role in cell motility and division. The ECM is a complex structural entity surrounding and supporting cells in tissues, and it plays a role in the regulation of intercellular communication, apoptosis, angiogenesis and cell differentiation [86]. Many proteins of the cytoskeleton and ECM interact with each other, and they were mostly decreased in both the moribund and survivor fish. Of these, collagens (_col1a1_, _col1a2_, _col1a3_, _col2a1_, _col5a1_, _col5a2_, _col6a1_, _col11a1_ and _col12a1_), myosins (_mybph_ and _mybpc2_), myomosins (_myom1_ and _myom2_) and actins (_actc1_ and _actn3_) decreased after _A. salmonicida_ infection. Further, serpin family h member 1 (_serpin1_), a collagen-specific chaperon, was also down-regulated in both groups. However, there were also some genes encoding myosins and myozenin, such as _mykl2_, _my1d_, _my06_ and _myoz2_, that showed up-regulation in 2 dpi and 6 dpi, respectively. Tropomyosin 3 (_tpm3_) was differentially regulated depending on the transcript type in both groups. Moreover, metalloproteinases (_mmp9_, _mmp13_ and _mmp19_) were up-regulated in both the 2 dpi and 6 dpi groups. Metalloproteinases are endopeptidase, produced by macrophages, and neutrophils, which are involved in tissue turnover, the degradation of ECM components and inflammatory response [87].